Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.1.1 (hexokinase)
5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of thyroxine on the activities of enzymes of energy metabolism (hexokinase, 6-phosphofructokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase, cytochrome c oxidase) was investigated in bone marrow myeloid cells and blood neutrophils of 3-10-day old neonatal piglets. Data obtained suggest different responsiveness of energy metabolism enzymes to thyroxine action. Repeated hormone injections resulted in the preferential stimulation of enzymes involved in oxidative stages of carbohydrate catabolism in animal myelocaryocytes, while the activities of anaerobic enzymes in these cells were less affected. At the same time glycolytic enzymes in neutrophil granulocytes showed higher sensitivity to thyroxine action than enzymes catalyzing oxidative stages of energy metabolism.
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PMID:[Effect of thyroxine on the activity of some enzymes of energy metabolism in bone marrow myeloid cells and blood neutrophils from piglets]. 1088 37

Glycolytic fibres in rat extensor digitorum longus (EDL) and tibialis anterior (TA) were selectively activated, as demonstrated by glycogen depletion, by indirect electrical stimulation via electrodes implanted in the vicinity of the peroneal nerve using high frequency (40 Hz) trains (250 ms at 1 Hz) and low voltage (threshold of palpable contractions). This regime was applied 10 times per day, each bout being of 15 min duration with 60 min recovery, for 2 weeks. Cryostat sections of muscles were stained for alkaline phosphatase to depict capillaries, succinate dehydrogenase (SDH) to demonstrate oxidative fibres, and periodic acid-Schiff reagent (PAS) to verify glycogen depletion. Specific activity of hexokinase (HK), 6-phosphofructokinase, pyruvate kinase, glycogen phosphorylase and cytochrome c oxidase (COX) were estimated separately in homogenates of the EDL and the predominantly glycolytic cortex and oxidative core of the TA. Stimulation increased the activity of HK but not that of oxidative enzymes in fast muscles. Comparison of changes in oxidative capacity and capillary supply showed a dissociation in the predominantly glycolytic TA cortex. Here, COX was 3.9+/-0.68 microM min(-1) (g wet wt)-1 in stimulated muscles compared with 3.7+/-0.52 microM min(-1) (g wet wt)-1 in contralateral muscles (difference not significant), while the percentage of oxidative fibres (those positively stained for SDH) was also similar in stimulated (14.0+/-2.8 %) and contralateral (12.2 +/-1.9 %) muscles. In contrast, the capillary to fibre ratio was significantly increased (2.01+/-0.12 vs. 1.55+/-0.04, P<0.01). We conclude that capillary supply can be increased independently of oxidative capacity, possibly due to haemodynamic factors, and serves metabolite removal to a greater extent than substrate delivery.
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PMID:Selective long-term electrical stimulation of fast glycolytic fibres increases capillary supply but not oxidative enzyme activity in rat skeletal muscles. 1103 8

After 14 generations of selection for voluntary wheel running, mice from the four replicate selected lines ran, on average, twice as many revolutions per day as those from the four unselected control lines. To examine whether the selected lines followed distinct strategies in the correlated responses of the size and metabolic capacities of the hindlimb muscles, we examined mice from selected lines, housed for 8 wk in cages with access to running wheels that were either free to rotate ("wheel access" group) or locked ("sedentary"). Thirteen of twenty individuals in one selected line (line 6) and two of twenty in another (line 3) showed a marked reduction ( approximately 50%) in total hindlimb muscle mass, consistent with the previously described expression of a small-muscle phenotype. Individuals with these "mini-muscles" were not significantly smaller in total body mass compared with line-mates with normal-sized muscles. Access to free wheels did not affect the relative mass of the mini-muscles, but did result in typical mammalian training effects for mitochondrial enzyme activities. Individuals with mini-muscles showed a higher mass-specific muscle aerobic capacity as revealed by the maximal in vitro rates of citrate synthase and cytochrome c oxidase. Moreover, these mice showed the highest activities of hexokinase and carnitine palmitoyl transferase. Females with mini-muscles showed the highest levels of phosphofructokinase, and males with mini-muscles the highest levels of pyruvate dehydrogenase. As shown by total muscle enzyme contents, the increase in mass-specific aerobic capacity almost completely compensated for the reduction caused by the "loss" of muscle mass. Moreover, the mini-muscle mice exhibited the lowest contents of lactate dehydrogenase and glycogen phosphorylase. Interestingly, metabolic capacities of mini-muscled mice resemble those of muscles after endurance training. Overall, our results demonstrate that during selection for voluntary wheel running, distinct adaptive paths that differentially exploit the genetic variation in morphological and physiological traits have been followed.
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PMID:Artificial selection for high activity favors mighty mini-muscles in house mice. 1252 84

Honeybees, Apis mellifera, gradually increase their rate of forage uptake as they gain foraging experience. This increase in foraging performance has been proposed to occur as a result of learning; however, factors affecting flight ability such as changes in physiological components of flight metabolism could also contribute to this pattern. Thus, the purpose of this study was to assess the contribution of physiological changes to the increase in honeybee foraging performance. We investigated aspects of honeybee flight muscle biochemistry throughout the adult life, from non-foraging hive bees, through young and mature foragers, to old foragers near the end of their lifespan. Two-dimensional gel proteomic analysis on honeybee thorax muscle revealed an increase in several proteins from hive bees to mature foragers including troponin T 10a, aldolase and superoxide dismutase. By contrast, the activities (V(max)) of enzymes involved in aerobic performance, phosphofructokinase, hexokinase, pyruvate kinase and cytochrome c oxidase, did not increase in the flight muscles of hive bees, young foragers, mature foragers and old foragers. However, citrate synthase activity was found to increase with foraging experience. Hence, our results suggest plasticity in both structural and metabolic components of flight muscles with foraging experience.
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PMID:Lifetime performance in foraging honeybees: behaviour and physiology. 1698 99

It is thought that glycolysis is the predominant energy pathway in cancer, particularly in solid and poorly vascularized tumors where hypoxic regions develop. To evaluate whether glycolysis does effectively predominate for ATP supply and to identify the underlying biochemical mechanisms, the glycolytic and oxidative phosphorylation (OxPhos) fluxes, ATP/ADP ratio, phosphorylation potential, and expression and activity of relevant energy metabolism enzymes were determined in multi-cellular tumor spheroids, as a model of human solid tumors. In HeLa and Hek293 young-spheroids, the OxPhos flux and cytochrome c oxidase protein content and activity were similar to those observed in monolayer cultured cells, whereas the glycolytic flux increased two- to fourfold; the contribution of OxPhos to ATP supply was 60%. In contrast, in old-spheroids, OxPhos, ATP content, ATP/ADP ratio, and phosphorylation potential diminished 50-70%, as well as the activity (88%) and content (3 times) of cytochrome c oxidase. Glycolysis and hexokinase increased significantly (both, 4 times); consequently glycolysis was the predominant pathway for ATP supply (80%). These changes were associated with an increase (3.3 times) in the HIF-1alpha content. After chronic exposure, both oxidative and glycolytic inhibitors blocked spheroid growth, although the glycolytic inhibitors, 2-deoxyglucose and gossypol (IC(50) of 15-17 nM), were more potent than the mitochondrial inhibitors, casiopeina II-gly, laherradurin, and rhodamine 123 (IC(50) > 100 nM). These results suggest that glycolysis and OxPhos might be considered as metabolic targets to diminish cellular proliferation in poorly vascularized, hypoxic solid tumors.
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PMID:Energy metabolism transition in multi-cellular human tumor spheroids. 1826 81

The objective of this study was to determine whether patients with chronic obstructive lung disease (COPD) display differences in organization of the metabolic pathways and segments involved in energy supply compared with healthy control subjects. Metabolic pathway potential, based on the measurement of the maximal activity (V(max)) of representative enzymes, was assessed in tissue extracted from the vastus lateralis in seven patients with COPD (age 67 +/- 4 yr; FEV(1)/FVC = 44 +/- 3%, where FEV(1) is forced expiratory volume in 1 s and FVC is forced vital capacity; means +/- SE) and nine healthy age-matched controls (age 68 +/- 2 yr; FEV(1)/FVC = 75 +/- 2%). Compared with control, the COPD patients displayed lower (P < 0.05) V(max) (mol.kg protein(-1).h(-1)) for cytochrome c oxidase (COX; 21.2 +/- 2.0 vs. 28.7 +/- 2.2) and 3-hydroxyacyl-CoA dehydrogenase (HADH; 2.54 +/- 0.14 vs. 3.74 +/- 0.12) but not citrate synthase (CS; 2.20 +/- 0.16 vs. 3.19 +/- 0.5). While no differences between groups were observed in V(max) for creatine phosphokinase, phosphorylase (PHOSPH), phosphofructokinase (PFK), pyruvate kinase, and lactate dehydrogenase, hexokinase (HEX) was elevated in COPD (P < 0.05). Enzyme activity ratios were higher (P < 0.05) for HEX/CS, HEX/COX, PHOSPH/HADH and PFK/HADH in COPD compared with control. It is concluded that COPD patients exhibit a reduced potential for both the electron transport system and fat oxidation and an increased potential for glucose phosphorylation while the potential for glycogenolysis and glycolysis remains normal. A comparison of enzyme ratios indicated greater potentials for glucose phosphorylation relative to the citric acid cycle and the electron transport chain and glycogenolysis and glycolysis relative to beta-oxidation.
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PMID:Organization of metabolic pathways in vastus lateralis of patients with chronic obstructive pulmonary disease. 1863 55

This study investigated the responses in substrate- and energy-based properties to repetitive days of prolonged submaximal exercise and recovery. Twelve untrained volunteers (Vo(2)(peak) = 44.8 +/- 2.0 ml.kg(-1).min(-1), mean +/- SE) cycled ( approximately 60 Vo(2)(peak)) on three consecutive days followed by 3 days of recovery. Tissue samples were extracted from the vastus lateralis both pre- and postexercise on day 1 (E1), day 3 (E3), and during recovery (R1, R2, R3) and were analyzed for changes in metabolism, substrate, and enzymatic and transporter responses. For the metabolic properties (mmol/kg(-1) dry wt), exercise on E1 resulted in reductions (P < 0.05) in phosphocreatine (PCr; 80 +/- 1.9 vs. 41.2 +/- 3.0) and increases (P < 0.05) in inosine monophosphate (IMP; 0.13 +/- 0.01 vs. 0.61 +/- 0.2) and lactate (3.1 +/- 0.4 vs. 19.2 +/- 4.3). At E3, both IMP and lactate were lower (P < 0.05) during exercise. For the transporters, the experimental protocol resulted in a decrease (P < 0.05) in glucose transporter-1 (GLUT1; 29% by R1), an increase in GLUT4 (29% by E3), and increases (P < 0.05) for both monocarboxylate transporters (MCT) (for MCT1, 23% by R2 and for MCT4, 18% by R1). Of the mitochondrial and cytosolic enzyme activities examined, cytochrome c oxidase (COX), and hexokinase were both reduced (P < 0.05) by exercise at E1 and in the case of hexokinase and phosphorylase by exercise on E3. With the exception at COX, which was lower (P < 0.05) at R1, no differences in enzyme activities existed at rest between E, E3, and recovery days. Results suggest that the glucose and lactate transporters are among the earliest adaptive responses of substrate and metabolic properties studied to the sudden onset of regular low-intensity exercise.
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PMID:Metabolic, enzymatic, and transporter responses in human muscle during three consecutive days of exercise and recovery. 1865 Mar 22

Honeybees, Apis mellifera, who show temporal polyethism, begin their adult life performing tasks inside the hive (hive bees) and then switch to foraging when they are about 2-3 weeks old (foragers). Usually hive tasks require little or no flying, whereas foraging involves flying for several hours a day and carrying heavy loads of nectar and pollen. Flight muscles are particularly plastic organs that can respond to use and disuse, and accordingly it would be expected that adjustments in flight muscle metabolism occur throughout a bee's life. We thus investigated changes in lifetime flight metabolic rate and flight muscle biochemistry of differently aged hive bees and of foragers with varying foraging experience. Rapid increases in flight metabolic rates early in life coincided with a switch in troponin T isoforms and increases in flight muscle maximal activities (V (max)) of the enzymes citrate synthase, cytochrome c oxidase, hexokinase, phosphofructokinase, and pyruvate kinase. However, further increases in flight metabolic rate in experienced foragers occurred without additional changes in the in vitro V (max) of these flight muscle metabolic enzymes. Estimates of in vivo flux (v) compared to maximum flux of each enzyme in vitro (fractional velocity, v/V (max)) suggest that most enzymes operate at a higher fraction of V (max) in mature foragers compared to young hive bees. Our results indicate that honeybees develop most of their flight muscle metabolic machinery early in life. Any further increases in flight metabolism with age or foraging experience are most likely achieved by operating metabolic enzymes closer to their maximal flux capacity.
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PMID:Lifetime- and caste-specific changes in flight metabolic rate and muscle biochemistry of honeybees, Apis mellifera. 1957 58

To develop new and more efficient anti-cancer strategies it will be important to characterize the products of transcription factor activity essential for tumorigenesis. One such factor is hypoxia-inducible factor-1alpha (HIF-1alpha), a transcription factor induced by low oxygen conditions and found in high levels in malignant solid tumors, but not in normal tissues or slow-growing tumors. In fast-growing tumors, HIF-1alpha is involved in the activation of numerous cellular processes including resistance against apoptosis, over-expression of drug efflux membrane pumps, vascular remodeling and angiogenesis as well as metastasis. In cancer cells, HIF-1alpha induces over-expression and increased activity of several glycolytic protein isoforms that differ from those found in non-malignant cells, including transporters (GLUT1, GLUT3) and enzymes (HKI, HKII, PFK-L, ALD-A, ALD-C, PGK1, ENO-alpha, PYK-M2, LDH-A, PFKFB-3). The enhanced tumor glycolytic flux triggered by HIF-1alpha also involves changes in the kinetic patterns of expressed isoforms of key glycolytic enzymes. The HIF-1alpha induced isoforms provide cancer cells with reduced sensitivity to physiological inhibitors, lower affinity for products and higher catalytic capacity (Vmax(f)) in forward reactions because of marked over-expression compared to those isoforms expressed in normal tissues. Some of the HIF1alpha-induced glycolytic isoforms also participate in survival pathways, including transcriptional activation of H2B histone (by LDH-A), inhibition of apoptosis (by HKII) and promotion of cell migration (by ENO-alpha). HIF-1alpha action may also modulate mitochondrial function and oxygen consumption by inactivating the pyruvate dehydrogenase complex in some tumor types, or by modulating cytochrome c oxidase subunit 4 expression to increase oxidative phosphorylation in other cancer cell lines. In this review, the roles of HIF-1alpha and HIF1alpha-induced glycolytic enzymes are examined and it is concluded that targeting the HIF1alpha-induced glucose transporter and hexokinase, important to glycolytic flux control, might provide better therapeutic targets for inhibiting tumor growth and progression than targeting HIF1alpha itself.
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PMID:HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. 1968 5

In a paper by Amat et al. (Modification of the intrinsic fluorescence and biochemical behavior of adenosine triphosphate ATP after irradiation with visible and near-infrared laser light, J. Photochem. Photobiol. B 81 (2005) 26-32) it was shown that the conversion of glucose to glucose-6-phosphate by hexokinase in vitro was accelerated when ATP, which supplies the reaction with energy, was priorly irradiated at non-resonant optical frequencies (NROF, i.e., 655 and 830 nm). Correspondingly, the authors postulated that NROF may lower the energy barrier for the dephosphorylation of ATP's terminal phosphate and thus accelerate the reaction rate through a more expeditious energy delivery. Next to the established photobiostimulatory influence of visible light on cells, which is mediated by cytochrome c oxidase through resonant effects of light, Amat et al. posited an interesting theory with which the same processes could be induced through non-resonant effects. To investigate the effects of NROF with respect to the hexokinase reaction in greater detail, the reaction rates were measured spectrofluorometrically after 633-nm laser irradiation of ATP, the ATP-Mg complex, hexokinase, and the entire reaction mixture at room temperature (22 degrees C) and at the optimal reaction temperature (30 degrees C). No differences in reaction rates between the NROF-irradiated and control groups were found at either temperature. The hypothesis that NROF enhances in vitro hexokinase activity by lowering the activation energy for the dephosphorylation of ATP's terminal phosphate by hexokinase was therefore disproven. Consequently, it is questionable, albeit not unequivocal, that NROF exerts an effect on other ATP-driven reactions in cell metabolic pathways through a direct impact on ATP.
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PMID:Absence of 633-nm laser irradiation-induced effects on glucose phosphorylation by hexokinase. 2020 88


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